Yield, NNS and prevalence of screening for DM and hypertension among pulmonary tuberculosis index cases and contacts through single time screening: A contact tracing-based study

Introduction Diabetes mellitus (DM), hypertension and pulmonary tuberculosis (PTB) are catastrophic illnesses that collectively lead to increased mortality and premature death. However, the size of the problem and the appropriate approach to deal with the burden is still unclear. We aimed to evaluate the yield, number needed to screen (NNS) to prevent one death or adverse event for screening DM and hypertension and assess the prevalence and contributors to DM and/or hypertension. Methods Based on PTB contact tracing, a cross-sectional study was conducted among 801 PTB index cases and 972 household contacts from April 2019 to October 2020 in Guizhou, China. All the participants were screened for DM and hypertension. The yield was calculated as the proportion of newly detected cases among the study subjects, excluding known cases. The NNS was computed by dividing the number needed to treat for risk factors by the prevalence of the unrecognized diseases. The univariate and multivariate logistic regression analyses were applied to determine the independent predictors of DM and/or hypertension. Results Of the 1,773 participants, the prevalence of DM and hypertension was 8.7% (70/801) and 15.2% (122/801) in the PTB patients, 3.2% (31/972) and 14.0% (136/972) in the contacts, respectively. The prevalence of DM and/or hypertension was 21.2% (170/801) among the PTB patients and 15.4% (150/972) among their contacts. The screening yields to detect new cases of DM and hypertension among PTB patients were 1.9% and 5.2%, and that in the contacts were 0.8% and 4.8%, respectively. The NNS for DM was 359 for the PTB cases and 977 for the contacts, 299 for PTB cases and 325 for hypertension, respectively. Older age, under or overweight and obesity, family history hypertension and earlier diagnosis of other chronic conditions were the independent predictors for DM and/or hypertension among both PTB cases and their contacts. Conclusion Screening for DM and hypertension should be mandated in PTB patients and their household contacts to disclose undetected cases of these two conditions during TB contact tracing, which might reduce the potential cardiovascular disease deaths.

indicates some NCDs patients are undiagnosed and untreated, probably leading to a lot of complications, even premature deaths. However, little is known about the precise size of the problem and the appropriate approach to deal with the burden is still unclear.
Disease screening is considered to produce yield both in the clinical field and public health.
Yield is the measure of previously unrecognized disease, diagnosed as the result of screening and brought to treatment [11]. At the same time, clarifying how many people should be detected to save one life is important. The number needed to screen (NNS) is the number of people that needed to screen for a given duration to prevent one death or adverse event [12]. If the yield is of high value and the NNS is small, the screening is supposed to be relatively costeffective. Both the yield and NNS of screening for DM and hypertension have rarely been evaluated in the settings of PTB control programs. Recently, screening for DM and hypertension in PTB patients is increasing [9,13,14]. It is important to clarify the magnitude of the yield and the NNS for screening DM and hypertension among the community people and PTB population. However, it is difficult to directly compare the problems between the PTB patients and the general population due to the limited actual conditions. In terms of the current well-established household contact tracing program for PTB patients, we assumed that the yield and NNS of screening in contacts of PTB cases are similar to that in the general population. Therefore, We will conduct a large-scale study based on household contact-tracing among TB households with a TB case.

Objective(s) of the study
To evaluate the yield, number needed to screen to prevent one death or adverse event (NNS) for screening DM and hypertension and assess the prevalence and contributors to DM and/or hypertension.

Study design
This is a cross-sectional study based on a PTB contact-trace program conducted from April 1, 2019 to October 30, 2020 in Guizhou, China, which is located in Guizhou province and stands the top 4 highest burdens of tuberculosis with high burden of NCDs in China.

Target population
Tuberculosis patients and their household contacts.

Inclusion criteria PTB index cases:
Newly diagnosed TB cases aged 15 years or more and currently on treatment for a duration of 0-6 months and notified to the National Tuberculosis Program from the study site were consecutively retrieved.
Household contact: Aged 15 years or more, lived in the same house with an index TB patient for more than 6 hours per week [15] between 3 months earlier than the diagnosis of the TB index case and 14 days after the TB index case initiating anti-tuberculosis treatment.

Exclusion criteria
Pregnant women, mentally disabled persons, and those living alone were excluded from the analysis.

Discontinuation criteria
All the subjects are free to withdraw off this study if they do not to continue anymore. In addition, if they are not suitable to continue, such as other sudden illness or events or accidents occurring, they are free to withdraw off this study. It is unlikely to terminate unless there is a natural disaster or any other special events.

Sample size calculation
This is a cross-sectional study based on a TB contact-trace study, which will be conducted in Guizhou, China from April 1, 2019 to October 30, 2020. Totally, 116 villages/communities with high PTB incidence in Guizhou will be drawn as the study sites. We consider that the chances of having DM or HTN were more similar among household members than the general population. This requires adjusting of the sample size with design effect (deff) [16][17][18], the value of which is assumed as 2.0 in this study. Eventually, the minimum sample size would be computed using the infinite population proportion formula with a continuity correction as shown below. Method(s) to minimize bias(es) during study: Inclusion criteria and exclusion criteria will be performed strictly to control selection of subjects. During fieldwork investigation, induced question will be avoided to obtain intentional answer. Obscure answer is required to clarify through phone call, Internet or other methods.

Study procedure
Initially, newly diagnosed PTB cases aged 15 years or more and notified to the National Tuberculosis Program from the study site will be consecutively retrieved according to the inclusion criteria.
During the eligible patients monthly visiting the hospital to obtain their medications, TB medical staff will contact the patients to obtain informed consent and make an appointment with them for home visits.1-3 household contacts aged 15 years or more per household in home visits. Simple random sampling method will be used to select the contacts when there will be more than three adult contacts per household. Meanwhile, all the enumerated contacts will be surveyed if there were three or fewer contacts.
DM and/or hypertension will be screened by assessing systolic/diastolic (SBP/DBP) blood pressure and fasting plasma glucose/random plasma glucose (FPG/RPG) among all participants following the world health organization (WHO) standard criteria. Those with different diseases identified from the study will be transferred to the local hospitals to undergoing the related treatment based on their physical situation. Those with known diseases who have previously lapsed from treatment will be suggested to access their local hospital to continue medical services.

Statistical analysis
Data obtained from the questionnaires and medical record review will be entered into EpiData software and R software will be employed for the statistical analysis. Student's t-test or ANOVA will be used to compare age, FPG/RPG and SBP/DBP among groups as appropriate and summarized using the mean and standard deviation. For continuous variables when data are not normally distributed, the nonparametric Mann-Whitney U test will be employed. Chisquare or Fisher exact tests will be applied for categorical variates where appropriate. The univariate analysis and the multivariate logistic regression model to determine the associated factors, and will be shown through forest plots [20]. The yield was calculated by dividing number of newly detected disease by the number of subject screened excluding those known to be diseased. NNS was computed as described somewhere [21], [22].

Ethical consideration
The proposal will be approved by both the Institutional Ethics Committee of Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand, as well as the Ethics Committee of Guizhou Provincial Center for Disease Prevention and Control before the study is conducted.
All proposed patients or citizens will have the right to agree or disagree to participate in the study and present using the informed consent. The anonymity and confidentiality will be maintained stringently throughout the study.

Limitation(s) and barrier(s) of the study (If applicable)
To date, no limitations and barriers are found.